Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep

2000 ◽  
Vol 89 (1) ◽  
pp. 192-199 ◽  
Author(s):  
X. S. Zhou ◽  
S. Shahabuddin ◽  
B. R. Zahn ◽  
M. A. Babcock ◽  
M. S. Badr
Keyword(s):  
Mechanical Ventilation ◽  
Sleep Apnea ◽  
Gender Difference ◽  
Minute Ventilation ◽  
Regression Line ◽  
Recovery Period ◽  
Premenopausal Women ◽  
Nrem Sleep ◽  
Central Apnea ◽  
End Tidal

We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25–35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21–43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (Vt) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal Pco 2(Pet CO2 ) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in Vt to 155 ± 29% (mean ± SD) and a reduction of Pet CO2 by −4.72 ± 0.57 Torr. In men, induction of a central apnea required an increase in Vt to 142 ± 13% and a reduction of Pet CO2 by −3.54 ± 0.31 Torr ( P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.

Effect of testosterone on the apneic threshold in women during NREM sleep

2003 ◽  
Vol 94 (1) ◽  
pp. 101-107 ◽  
Author(s):  
X. S. Zhou ◽  
J. A. Rowley ◽  
F. Demirovic ◽  
M. P. Diamond ◽  
M. S. Badr
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Premenopausal Women ◽  
Nrem Sleep ◽  
Central Apnea ◽  
Rapid Eye Movement Sleep ◽  
A Value ◽  
Before And After ◽  
Testosterone Administration ◽  
End Tidal

The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10–12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%V˙e) was plotted against the change in end-tidal CO2(Pet CO2 ); %V˙e was given a value of zero during central apnea. The AT was defined as the Pet CO2 at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression V˙e vs. Pet CO2 . Both the AT (39.5 ± 2.9 vs. 42.1 ± 3.0 Torr; P = 0.002) and HPVR (0.20 ± 0.05 vs. 0.33 ± 0.11%V˙e/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.

scholarly journals Sustained hyperoxia stabilizes breathing in healthy individuals during NREM sleep

2010 ◽  
Vol 109 (5) ◽  
pp. 1378-1383 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Prabhat Sinha ◽  
Sukanya Pranathiageswaran ◽  
M. Safwan Badr
Keyword(s):  
Mechanical Ventilation ◽  
Ventilatory Response ◽  
Random Order ◽  
Nrem Sleep ◽  
Minimal Change ◽  
Central Apnea ◽  
Noninvasive Mechanical Ventilation ◽  
Healthy Individuals ◽  
Air Exposure ◽  
End Tidal

The present study was designed to determine whether hyperoxia would lower the hypocapnic apneic threshold (AT) during non-rapid eye movement (NREM) sleep. Nasal noninvasive mechanical ventilation was used to induce hypocapnia and subsequent central apnea in healthy subjects during stable NREM sleep. Mechanical ventilation trials were conducted under normoxic (room air) and hyperoxic conditions (inspired Po2 > 250 Torr) in a random order. The CO2 reserve was defined as the minimal change in end-tidal Pco2 (PetCO2) between eupnea and hypocapnic central apnea. The PetCO2 of the apnea closest to eupnea was designated as the AT. The hypocapnic ventilatory response was calculated as the change in ventilation below eupnea for a given change in PetCO2. In nine participants, compared with room air, exposure to hyperoxia was associated with a significant decrease in eupneic PetCO2 (37.5 ± 0.6 vs. 41.1 ± 0.6 Torr, P = 0.001), widening of the CO2 reserve (−3.8 ± 0.8 vs. −2.0 ± 0.3 Torr, P = 0.03), and a subsequent decline in AT (33.3 ± 1.2 vs. 39.0 ± 0.7 Torr; P = 001). The hypocapnic ventilatory response was also decreased with hyperoxia. In conclusion, 1) hyperoxia was associated with a decreased AT and an increase in the magnitude of hypocapnia required for the development of central apnea. 2) Thus hyperoxia may mitigate the effects of hypocapnia on ventilatory motor output by lowering the hypocapnic ventilatory response and lowering the resting eupneic PetCO2, thereby decreasing plant gain.

Upper airway muscle responsiveness to rising Pco 2 during NREM sleep

2000 ◽  
Vol 89 (4) ◽  
pp. 1275-1282 ◽  
Author(s):  
Giora Pillar ◽  
Atul Malhotra ◽  
Robert B. Fogel ◽  
Josee Beauregard ◽  
David I. Slamowitz ◽  
...  
Keyword(s):  
Muscle Activation ◽  
Slow Wave Sleep ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Dilator Muscle ◽  
Pharyngeal Muscles ◽  
Stage 2 Sleep ◽  
Significant Change ◽  
End Tidal

Although pharyngeal muscles respond robustly to increasing Pco 2 during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO2-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal Pco 2(Pet CO2 ) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO2(Pet CO2 = 6 Torr above the eupneic level) were also assessed during SWS ( n = 9) or stage 2 sleep ( n = 7). Pet CO2 increased spontaneously by 0.8 ± 0.1 Torr from stage 2 to SWS (from 43.3 ± 0.6 to 44.1 ± 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 ± 0.1 to 11.9 ± 0.3 l/min in stage 2 and 8.6 ± 0.4 to 12.7 ± 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of Pet CO2 (50.4 ± 1.6 Torr in stage 2, and 50.4 ± 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.

scholarly journals Compensatory responses to upper airway obstruction in obese apneic men and women

2012 ◽  
Vol 112 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Chien-Hung Chin ◽  
Jason P. Kirkness ◽  
Susheel P. Patil ◽  
Brian M. McGinley ◽  
Philip L. Smith ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Airway Obstruction ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Upper Airway Obstruction ◽  
Men And Women ◽  
Compensatory Responses ◽  
Obstructive Sleep

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age ( n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow ( P = 0.003) and inspiratory duty cycle ( P = 0.017) in response to prolonged periods of UAO and an ∼20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) ( P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.

scholarly journals Effect of episodic hypoxia on the susceptibility to hypocapnic central apnea during NREM sleep

2010 ◽  
Vol 108 (2) ◽  
pp. 369-377 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Irina Shanidze ◽  
Lisa Pierchala ◽  
Daniel Belen ◽  
Jason H. Mateika ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Ventilatory Response ◽  
Recovery Period ◽  
Positive Pressure ◽  
Central Apnea ◽  
Hypoxic Ventilatory Response ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Long Term Facilitation

We hypothesized that episodic hypoxia (EH) leads to alterations in chemoreflex characteristics that might promote the development of central apnea in sleeping humans. We used nasal noninvasive positive pressure mechanical ventilation to induce hypocapnic central apnea in 11 healthy participants during stable nonrapid eye movement sleep before and after an exposure to EH, which consisted of fifteen 1-min episodes of isocapnic hypoxia (mean O2 saturation/episode: 87.0 ± 0.5%). The apneic threshold (AT) was defined as the absolute measured end-tidal Pco2 (PetCO2) demarcating the central apnea. The difference between the AT and baseline PetCO2 measured immediately before the onset of mechanical ventilation was defined as the CO2 reserve. The change in minute ventilation (V̇I) for a change in PetCO2 (ΔV̇I/ ΔPetCO2) was defined as the hypocapnic ventilatory response. We studied the eupneic PetCO2, AT PetCO2, CO2 reserve, and hypocapnic ventilatory response before and after the exposure to EH. We also measured the hypoxic ventilatory response, defined as the change in V̇I for a corresponding change in arterial O2 saturation (ΔV̇I/ΔSaO2) during the EH trials. V̇I increased from 6.2 ± 0.4 l/min during the pre-EH control to 7.9 ± 0.5 l/min during EH and remained elevated at 6.7 ± 0.4 l/min the during post-EH recovery period ( P < 0.05), indicative of long-term facilitation. The AT was unchanged after EH, but the CO2 reserve declined significantly from −3.1 ± 0.5 mmHg pre-EH to −2.3 ± 0.4 mmHg post-EH ( P < 0.001). In the post-EH recovery period, ΔV̇I/ΔPetCO2 was higher compared with the baseline (3.3 ± 0.6 vs. 1.8 ± 0.3 l·min−1·mmHg−1, P < 0.001), indicative of an increased hypocapnic ventilatory response. However, there was no significant change in the hypoxic ventilatory response (ΔV̇I/ΔSaO2) during the EH period itself. In conclusion, despite the presence of ventilatory long-term facilitation, the increase in the hypocapnic ventilatory response after the exposure to EH induced a significant decrease in the CO2 reserve. This form of respiratory plasticity may destabilize breathing and promote central apneas.

Apnea after normocapnic mechanical ventilation during NREM sleep

1994 ◽  
Vol 77 (5) ◽  
pp. 2079-2085 ◽  
Author(s):  
A. M. Leevers ◽  
P. M. Simon ◽  
J. A. Dempsey
Keyword(s):  
Mechanical Ventilation ◽  
Nrem Sleep ◽  
Inspiratory Effort ◽  
Control Mechanical Ventilation ◽  
Inhibitory Effects ◽  
Inspiratory Motor ◽  
Ventilator Mode ◽  
Controlled Mechanical Ventilation ◽  
The Subject ◽  
End Tidal

We determined whether normocapnic mechanical ventilation at high tidal volume (VT) and breathing frequency (f) during non-rapid-eye-movement (NREM) sleep would cause apnea. Seven normal sleeping subjects were placed on assist-control mechanical ventilation (i.e., subject initiates inspiration) and VT was gradually increased to 2.1 times eupneic VT (1.17 +/- 0.04 liters). This high VT was maintained for 5 min, the ventilator mode was switched to controlled mechanical ventilation, and f was increased gradually from 9.5 +/- 1.0 (during assist-control mechanical ventilation) to 14.0 +/- 0.7 breaths/min. Normocapnia (end-tidal PCO2 = 44 +/- 1.2 Torr) was maintained throughout the trials. Inspiratory effort was completely inhibited during the period of sustained high VT and f, and apnea occurred immediately after cessation of the passive mechanical ventilation. The duration of the apnea preceding the first inspiratory effort was 20.3 +/- 2.3 s or 7.1 times the eupneic expiratory duration and 5 times the expiratory duration chosen by the subject during assist-control mechanical ventilation. We conclude that inhibition of inspiratory motor output occurs during and after normocapnic mechanical ventilation at high VT and f during NREM sleep. These neuromechanical inhibitory effects may serve to initiate and prolong apnea.

Determinants of poststimulus potentiation in humans during NREM sleep

1992 ◽  
Vol 73 (5) ◽  
pp. 1958-1971 ◽  
Author(s):  
M. S. Badr ◽  
J. B. Skatrud ◽  
J. A. Dempsey
Keyword(s):  
Eye Movement ◽  
Control Period ◽  
Periodic Breathing ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Central Apnea ◽  
Inhibitory Effects ◽  
Arterial Pco2 ◽  
End Tidal ◽  
Sustained Hypoxia

To test whether active hyperventilation activates the “afterdischarge” mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.

Cerebral hypoperfusion modifies the respiratory chemoreflex during orthostatic stress

2013 ◽  
Vol 125 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Shigehiko Ogoh ◽  
Hidehiro Nakahara ◽  
Kazunobu Okazaki ◽  
Damian M. Bailey ◽  
Tadayoshi Miyamoto
Keyword(s):  
Lower Body Negative Pressure ◽  
Minute Ventilation ◽  
Regression Line ◽  
Cerebral Hypoperfusion ◽  
Orthostatic Stress ◽  
Respiratory Chemoreflex ◽  
Underlying Mechanisms ◽  
End Tidal ◽  
Induced Changes ◽  
The Relationship

The respiratory chemoreflex is known to be modified during orthostatic stress although the underlying mechanisms remain to be established. To determine the potential role of cerebral hypoperfusion, we examined the relationship between changes in MCA Vmean (middle cerebral artery mean blood velocity) and V̇E (pulmonary minute ventilation) from supine control to LBNP (lower body negative pressure; −45mmHg) at different CO2 levels (0, 3.5 and 5% CO2). The regression line of the linear relationship between V̇E and PETCO2 (end-tidal CO2) shifted leftwards during orthostatic stress without any change in sensitivity (1.36±0.27 l/min per mmHg at supine to 1.06±0.21 l/min per mmHg during LBNP; P=0.087). In contrast, the relationship between MCA Vmean and PETCO2 was not shifted by LBNP-induced changes in PETCO2. However, changes in V̇E from rest to LBNP were more related to changes in MCA Vmean than changes in PETCO2. These findings demonstrate for the first time that postural reductions in CBF (cerebral blood flow) modified the central respiratory chemoreflex by moving its operating point. An orthostatically induced decrease in CBF probably attenuated the ‘washout’ of CO2 from the brain causing hyperpnoea following activation of the central chemoreflex.

Effect of episodic hypoxia on upper airway mechanics in humans during NREM sleep

2002 ◽  
Vol 92 (6) ◽  
pp. 2565-2570 ◽  
Author(s):  
Mahdi Shkoukani ◽  
Mark A. Babcock ◽  
M. Safwan Badr
Keyword(s):  
Minute Ventilation ◽  
Recovery Period ◽  
Control Period ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Hypoxic Exposure ◽  
Airway Mechanics ◽  
Episodic Hypoxia ◽  
Long Term Facilitation

We hypothesized that long-term facilitation (LTF) is due to decreased upper airway resistance (Rua). We studied 11 normal subjects during stable non-rapid eye movement sleep. We induced brief isocapnic hypoxia (inspired O2fraction = 8%) (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 20 min of recovery (R20) for ventilation, timing, and Rua. In addition, nine subjects were studied in a sham study with no hypoxic exposure. During the episodic hypoxia study, inspiratory minute ventilation (V˙i) increased from 7.1 ± 1.8 l/min during the control period to 8.3 ± 1.8 l/min at R20 (117% of control; P < 0.05). Conversely, there was no change in diaphragmatic electromyogram (EMGdia) between control (16.1 ± 6.9 arbitrary units) and R20 (15.3 ± 4.9 arbitrary units) (95% of control; P > 0.05). In contrast, increasedV˙i was associated with decreased Rua from 10.7 ± 7.5 cmH2O · l−1 · s during control to 8.2 ± 4.4 cmH2O · l−1 · s at R20 (77% of control; P < 0.05). No change was noted in V˙i, Rua, or EMGdia during the recovery period relative to control during the sham study. We conclude the following: 1) increased V˙i in the recovery period is indicative of LTF, 2) the lack of increased EMGdia suggests lack of LTF to the diaphragm, 3) reduced Rua suggests LTF of upper airway dilators, and 4) increased V˙i in the recovery period is due to “unloading” of the upper airway by LTF of upper airway dilators.

scholarly journals Tetraplegia is a risk factor for central sleep apnea

2014 ◽  
Vol 116 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Abdulghani Sankari ◽  
Amy T. Bascom ◽  
Susmita Chowdhuri ◽  
M. Safwan Badr
Keyword(s):  
Risk Factor ◽  
Sleep Apnea ◽  
Central Sleep Apnea ◽  
Control Group ◽  
Apnea Hypopnea Index ◽  
Central Apnea ◽  
Cord Injury ◽  
Before And After ◽  
The Difference ◽  
End Tidal

Sleep-disordered breathing (SDB) is highly prevalent in patients with spinal cord injury (SCI); the exact mechanism(s) or the predictors of disease are unknown. We hypothesized that patients with cervical SCI (C-SCI) are more susceptible to central apnea than patients with thoracic SCI (T-SCI) or able-bodied controls. Sixteen patients with chronic SCI, level T6 or above (8 C-SCI, 8 T-SCI; age 42.5 ± 15.5 years; body mass index 25.9 ± 4.9 kg/m2) and 16 matched controls were studied. The hypocapnic apneic threshold and CO2 reserve were determined using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal CO2 (PetCO2) before and after. Steady-state plant gain (PG) was calculated from PetCO2 and VE ratio during stable sleep. Controller gain (CG) was defined as the ratio of change in VE between control and hypopnea or apnea to the ΔPetCO2. Central SDB was more common in C-SCI than T-SCI (63% vs. 13%, respectively; P < 0.05). Mean CO2 reserve for all participants was narrower in C-SCI than in T-SCI or control group (−0.4 ± 2.9 vs.−2.9 ± 3.3 vs. −3.0 ± 1.2 l·min−1·mmHg−1, respectively; P < 0.05). PG was higher in C-SCI than in T-SCI or control groups (10.5 ± 2.4 vs. 5.9 ± 2.4 vs. 6.3 ± 1.6 mmHg·l−1·min−1, respectively; P < 0.05) and CG was not significantly different. The CO2 reserve was an independent predictor of apnea-hypopnea index. In conclusion, C-SCI had higher rates of central SDB, indicating that tetraplegia is a risk factor for central sleep apnea. Sleep-related hypoventilation may play a significant role in the mechanism of SDB in higher SCI levels.

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